The Effect of Chlorogenic Acid Enriched Coffee on Glucose Absorption in Healthy Volunteers and Its Effect on Body Mass When Used Long-term in Overweight and Obese People

Abstract

The results from a clinical study performed in 12 healthy volunteers with different coffee products containing glucose show that instant coffee enriched with chlorogenic acid induced a reduction in the absorption of glucose of 6.9% compared with the control. No such effects were seen with normal or decaffeinated instant coffee. In a second, comparative, randomized, double-blind, 12-week study we investigated the effect on the body mass of 30 overweight people, compared with normal instant coffee. The average losses in mass in the chlorogenic acid enriched and normal instant coffee groups were 5.4 and 1.7 kg, respectively. We conclude that chlorogenic acid enriched instant coffee appears to have a significant effect on the absorption and utilization of glucose from the diet. This effect, if the coffee is used for an extended time, may result in reduced body mass and body fat when compared with the use of normal instant coffee.

Full text

The Journal of International Medical Research
2007; 35: 900 – 908
900
The Effect of Chlorogenic Acid Enriched
Coffee on Glucose Absorption in Healthy
Volunteers and Its Effect on Body Mass
When Used Long-term in Overweight and
Obese People
E THOM
ETC Research and Development, Oslo, Norway
The results from a clinical study
performed in 12 healthy volunteers with
different coffee products containing
glucose show that instant coffee enriched
with chlorogenic acid induced a reduction
in the absorption of glucose of 6.9%
compared with the control. No such effects
were seen with normal or decaffeinated
instant coffee. In a second, comparative,
randomized, double-blind, 12-week study
we investigated the effect on the body
mass of 30 overweight people, compared
with normal instant coffee. The average
losses in mass in the chlorogenic acid
enriched and normal instant coffee
groups were 5.4 and 1.7 kg, respectively.
Weconclude that chlorogenic acid
enriched instant coffee appears to have a
significant effect on the absorption and
utilization of glucose from the diet. This
effect, if the coffee is used for an extended
time, may result in reduced body mass
and body fat when compared with the use
of normal instant coffee.
KEY WORDS: CHLOROGENIC ACID; COFFEE; GLUCOSE; DIET
Introduction
Coffee is the world’s favourite beverage, with
an estimated 1.5 billion cups being drunk
every day. Despite decades of research on
coffee and centuries of consumption, there
are many misconceptions concerning the
potential health risks associated with it.1
Coffee is a complex mixture of chemicals
that provides significant amounts of
chlorogenic acid and caffeine. Unfiltered
coffee is a significant source of cafestol and
kahweol, which are diterpenes that have
been implicated in the cholesterol-raising
effects of coffee. The results of several
epidemiological studies suggest that coffee
may help prevent several chronic diseases,
including type-2 diabetes. Coffee
consumption is, however,associated with an
increase in several cardiovascular disease
risk factors, including raised blood pressure
and plasma homocysteine.2
Some groups, including people with
hypertension, children, adolescents and the
elderly, may be more vulnerable to the

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Chlorogenic acid enriched coffee and glucose absorption
adverse effects of caffeine (1,3,7-
trimethylxanthine). In addition, currently
available evidence suggests that it may be
prudent for pregnant women to limit coffee
consumption to 3 cups/day in order to provide
no more than 300 mg/day of caffeine,
thereby avoiding any increased probability
of spontaneous abortion or impaired fetal
growth.2Anumber of recent publications
have focused on the disease-preventive and
weight-reducing effects of coffee.3,4
From a pharmacological point of view,
coffee is an extremely complex substance. It
is a major source of caffeine, which is the
most widely consumed stimulant in the
world, and has been implicated in the
development of cardiovascular diseases such
as acute myocardial infarction. Coffee
contains a multitude of other substances,
however,many of which are potentially
biological active. It is also an extremely rich
source of chlorogenic acids.
The amounts of chlorogenic acids and
caffeine in coffee are comparable.5,6
Chlorogenic acids are an important group of
biologically active dietaryphenols; the best
known being 5-caffeoylquinic acid. The daily
intake of chlorogenic acids by coffee drinkers
is considered to be in the range 0.5 – 1.0 g5–7
and chlorogenic acids have been found to
exhibit antioxidant activity in vitro.7In
addition to their antioxidant effects, there has
been growing interest in the other biological
properties of phenolic compounds7 – 9 and
accumulating evidence suggests that certain
dietary phenols, through a variety of
mechanisms, may result in an altered
patternof intestinal glucose uptake.
Chlorogenic acids have been shown to
influence postprandial blood sugar
concentration, glucose tolerance, serum lipid
concentration and glucose absorption from
the intestine. They have been found to
reduce the intestinal absorption of glucose in
rats by encouraging dispersal of the Na+
electrochemical gradient, which draws
glucose into the enterocytes,10 and to inhibit
the activity of hepatic glucose-6-
phosphatase, which is implicated in glucose
homeostasis.11,12 This has been confirmed in
an in vivo study investigating chlorogenic
acid extracts from coffee, and their
derivatives, on blood sugar concentrations
and the secretion of an incretin, glucose-
dependent insulinotropic polypeptide (GIP).
The study showed that coffee (decaffeinated
or caffeinated) when compared with a
control drink, significantly attenuated the
postprandial release of GIP in the proximal
part of the small intestine. As the quantity of
glucose absorbed at the intestinal barrier
determines the magnitude of the GIP
response, these results suggest that coffee
decreases the absorption of glucose from the
small intestine.13,14
Based on this information, we carried out
clinical studies to: (i) investigate the effect of
chlorogenic acid supplemented coffee on the
glucose profile of healthy volunteers,
compared with that of normal coffee; and (ii)
evaluate the effect of chlorogenic acid
supplemented coffee when taken as part of a
regular diet in overweight and obese subjects.
Materials and methods
PRODUCTS USED
The test coffee product used in the studies
was Coffee Slender®(Med-Eq Ltd, Tønsberg,
Norway), packed in sachets each containing
2200 mg instant coffee (equal parts of
Arabica and Robusta coffees). A total of 200
mg per 2200 mg of the Coffee Slender®
product comprises an extract of green coffee,
obtained by a traditional process, from the
beans of Coffea canephora robusta Pierre
(Svetol®;Berkem SA, Gardonne, France). This
is particularly rich in chlorogenic acids (45 –
50% by weight [90 – 100 mg]), with equal

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Chlorogenic acid enriched coffee and glucose absorption
amounts of the three isomers, 5-, 4- and 3-
caffeoylquinic acid. The extraction process is
performed with alcohol as the solvent and
the extract contains < 2% caffeine, and is
also virtually free from cafestol and kahweol;
as mentioned earlier these latter two
substances might be linked to the cholesterol
raising effect of coffee.
Nescafé®Gold Norwegian blend
(caffeinated) and Nescafé®Gold Norwegian
blend decaffeinated instant coffee (Nestlé,
Vevey, Switzerland) were used as the
comparative products. The content of
chlorogenic acids is the same in both these
coffees, the literature indicating that instant
coffees contain 30 – 40 mg/g of chlorogenic
acid.13
STUDY 1
Study 1 investigated the effects of a single
drink of the different coffee products on the
absorption of glucose.
Volunteer recruitment, study design and
treatment
The volunteers recruited into the study were
healthy non-smokers, of normal weight
(body mass index [BMI] < 25.0 kg/m2)and
not taking any drugs on a regular basis for
the treatment of chronic diseases.
The study was designed as a three-way
double-blind randomized crossover study
with each subject serving as his or her own
control. The coffee products used were
packed in similar boxes in order to keep the
study blind. The different treatment regimes
were: (i) 25 g of sucrose in 400 ml of water
(control); (ii) 25 g of sucrose and 10 g of
Coffee Slender®in 400 ml water; (iii) 25 g of
sucrose and 10 g of normal instant coffee
(Nescafé®Gold Norwegian blend) in 400 ml
water; and (iv) 25 g of sucrose and 10 g of
decaffeinated instant coffee (Nescafé®Gold
Norwegian blend) in 400 ml water.
After overnight fasting an oral glucose
tolerance test (control) was performed on all
the volunteers. Glucose levels were followed
for 2 h after intake with measurement at 15,
30, 45, 60, 90 and 120 min and they were
then immediately randomized to one of the
treatments, with glucose levels again followed
for 2 h after intake with measurement at 15,
30, 45, 60, 90 and 120 min. There was a 1-
week washout period between the different
treatments, intake was always performed
after an overnight (12 h) fast, the fasting
glucose level was measured each time prior
to treatment, and glucose levels were always
followed for 2 h after each treatment and
measured at 15, 30, 45, 60, 90 and 120 min.
All participants gave written informed
consent before entering the study. A regional
ethics committee (REK East) approved the
study,which was conducted according to the
principles of the Declaration of Helsinki,
good clinical practice and local regulations.
Statistical analysis
Data were analysed by calculating the total
area under the curve (AUC) using the linear
trapezoidal rule. Significant differences
between plasma concentrations of glucose
were measured by using two-factor repeated
measures analysis of variance (ANOVA). A
P-value < 0.05 was considered to be
statistically significant.
STUDY 2
Study 2 was carried out to evaluate the effect
of several drinks of Coffee Slender®
compared with the effect of several drinks of
normal instant coffee on weight when taken
as part of a regular diet in slight to
moderately overweight volunteers.
Volunteer recruitment, study design and
treatment
The volunteers recruited into the study were

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Chlorogenic acid enriched coffee and glucose absorption
slightly to moderately overweight (BMI 27.5
–32.0 kg/m2)non-smokers not taking any
drugs on a regular basis for the treatment of
chronic diseases. They had been drinking
coffee daily before the study. All the
volunteers were asked to follow the same life-
style that they had prior to entering the
study and not to commence other weight loss
programmes whilst participating in the
study. They did not receive any information
on diet and were also told to maintain their
current physical exercise programme.
The study was designed as a randomized,
placebo-controlled study.Half of the
volunteers drank Coffee Slender®[five cups
(sachets)/day (11 g/day of coffee)] while the
other half drank normal Nescafé®Gold
Norwegian blend instant coffee [five
cups/day (11 g/day of coffee)]. The coffee in
both groups was taken black. The duration
of the study was 12 weeks and the volunteers
were also followed-up after 1 and 3 months.
Anthropometric measurements, including
height, mass and body fat composition were
made initially, and mass and body fat
composition measurements were repeated at
the two follow-up visits. The body mass of
the subjects wearing ordinarylight indoor
clothing without shoes was measured to an
accuracy of 0.1 kg and height was measured
to the nearest 0.5 cm. Body fat was measured
using bioimpedance equipment.
All volunteers gave written informed
consent before entering the study. A regional
ethics committee (REK East) approved the
study, which was conducted according to the
principles of the Declaration of Helsinki,
good clinical practice and local regulations.
Statistical analysis
Data were presented as means ± SD.
Student’s t-test (parametric test) or the
Mann–Whitney test (non-parametric test)
were used to compare differences between
values. Differences with a P-value < 0.05
were considered to be statistically significant.
Results
STUDY 1
Twelve healthy volunteers participated in
this study (six females, six males) with a
mean ± SD age of 24.2 ± 3.2 years and
normal weight (BMI < 25.0 kg/m2).
The mean plasma concentrations of
glucose after consumption of the four
beverages are shown in Table 1, and mean ±
SE data for AUC are shown in Table 2. The
AUC was 778 ± 10.2 mmol/l per min after
intake of the control, 724 ± 8.2 mmol/l per
min after intake of Coffee Slender®,788 ±
10.1 mmol/l per min after intake of normal
Nescafé®Gold Norwegian blend instant
(caffeinated) coffee and 818 ± 10.9 mmol/l
per min after intake of Nescafé®Gold
Norwegian blend instant decaffeinated
coffee. The reduction in AUC after intake of
Time after intake (min)
Beverage 0 15 30 45 60 90 120
Glucose solution (control) 5.48 7.00 8.36 7.48 6.50 5.76 5.25
Coffee Slender®5.23 5.82 6.50 7.50 6.23 5.76 5.00
Nescafé®instant coffee (caffeinated) 5.48 5.23 6.10 7.80 8.25 6.40 5.40
Nescafé®decaffeinated coffee 5.50 6.60 7.70 8.40 7.30 6.60 5.80
TABLE 1:
Mean plasma glucose concentrations (mmol/l) following intake of four different
beverages by 12 healthy volunteers

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Chlorogenic acid enriched coffee and glucose absorption
Coffee Slender®was, therefore, significantly
reduced compared with after intake of the
control beverage (P<0.05). No significant
effects were seen compared with the control
after intake of normal instant coffee or
decaffeinated instant coffee.
STUDY 2
Thirty volunteers (BMI 27.5 – 32.0 kg/m2)
were enrolled in this study; 15 received the
Coffee Slender®and the others received the
normal instant coffee (Nescafé®Gold
Norwegian blend).
Table 3 presents the anthropometric
parameters for the two groups of
participants, which reveals that both groups
were comparable at the start of the study
with respect to the parameters of interest.
Glucose Nescafé®Nescafé®
solution Coffee instant coffee decaffeinated
(control) Slender®(caffeinated) coffee
Plasma glucose AUC 778 ± 10.2 724 ± 8.2a788 ± 10.1 818 ± 10.9
aP<0.05 compared with control.
No. of Start weight BMI Height
Group volunteers (kg) (kg/m2) (cm) Gender
Coffee Slender®15 85.2 ± 4.5 29.2 ± 2.5 171 ± 5.2 8F/7M
Nescafé®instant coffee
(caffeinated) 15 84.3 ± 4.3 29.9 ± 2.4 168 ± 4.3 10F/5M
BMI, body mass index.
TABLE 2:
Mean ± SE area under the curve (AUC) data for plasma glucose concentration over the
120 min study period following intake of four different beverages by 12 healthy volunteers
TABLE 3:
Mean ± SD anthropometric parameters for overweight volunteers taking Coffee Slender®
(total 11 g/day) or Nescafé®instant coffee (total 11 g/day) for 12 weeks
Weight (kg)
Difference
Group Start Week 4 Week 12 (start – week 12) P-value
Coffee Slender®85.2 ± 4.5 83.6 ± 4.1 79.8 ± 3.9 5.4 ± 0.6 P<0.05a
Nescafé®instant coffee
(caffeinated) 84.3 ± 4.3 83.7 ± 4.1 82.6 ± 4.2 1.7 ± 0.9 NS
aThe difference in weight loss between the two groups was statistically significant (P<0.05) and the weight
loss in the Coffee Slender®group (start – week 12) was also statistically significant (P<0.05).
NS, not significant (P≥0.05).
TABLE 4:
Mean ± SD weight for overweight volunteers taking Coffee Slender®(total 11 g/day) or
Nescafé®instant coffee (total 11 g/day) for 12 weeks

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Chlorogenic acid enriched coffee and glucose absorption
Results from the weight study (Table 4)
show that the mean ± SD weight reductions
for Coffee Slender®and normal instant
coffee drinkers were 5.4 ± 0.6 and 1.7 ± 0.9
kg, respectively.The difference in weight loss
between the two groups was statistically
significant (P<0.05) and the weight loss in
the Coffee Slender®group by the end of study
was also statistically significant (P<0.05)
compared with the start.
During the study, the percentage of body
fat in the Coffee Slender®group showed a
statistically significant reduction from 27.2%
at the start to 23.6% at the end of the study.
This means that approximately 80% of the
weight reduction in the Coffee Slender®
group was due to loss of fat. Body fat
reduction in the group using instant coffee
did not reach statistical significance (Table 5).
All the participants completed the study
according to the protocol. The tolerability was
equally good in both groups and none of the
participants reported any side-effects that
could be related to the treatment they received.
Discussion
Obesity and overweight are serious health
problems in most industrialized countries
and different programmes have been
launched over the past decade to try and
cope with it. Despite these, however, the
average body weight of both males and
females is still increasing. Weight problems
can have a negative impact on quality of life
and, in the case of obesity,can even lead to
asignificant reduction in life expectancy.
With the exception of serious
neuroendocrine pathologies, weight
problems are mainly due to lifestyle.
There is a link between the amount of
dietary carbohydrates and the amount of fat
found in the adipose reserves. This is because
carbohydrates are responsible for most
calorific intake in the diet and their intake in
the formof sugars reduces the need for
calorific consumption from reserves as a
result of normal insulin production and
activity,ensuring that they are metabolized
first and not stored in the body.On the other
hand, if the amount of glucose in the blood
is in excess of what is required and hepatic
glycogenesis occurs, the excess glucose enters
into the adipocytes where it is stored as fat
reserves (activated by insulin in response to
hyperglycaemia). The consequences are that
the fat reserves are not used for energy and
an increase in adipocytes takes place.
During dieting, the lower intake of
carbohydrates forces the metabolism of fat
reserves deposited in the adipocytes,
Body fat (%)
Difference
Group Start Week 4 Week 12 (start – week 12) P-value
Coffee Slender®27.2 ± 2.0 25.6 ± 1.8 23.6 ± 1.7 3.6 ± 0.3 P<0.05
Nescafé®instant coffee
(caffeinated) 26.9 ± 2.1 26.7 ± 2.0 26.2 ± 2.0 0.7 ± 0.4 NS
aThe difference in loss of body fat between the two groups was statistically significant (P<0.05) and the loss
in the Coffee Slender®group (start – week 12) was also statistically significant (P<0.05).
NS, not significant (P≥0.05).
TABLE 5:
Mean ± SD percentage of body fat for overweight volunteers taking Coffee Slender®
(total 11 g/day) or Nescafé®instant coffee (total 11 g/day) for 12 weeks

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Chlorogenic acid enriched coffee and glucose absorption
resulting in weight loss. It is possible to
improve the effects of reduced consumption
of carbohydrate by exploiting hepatic
activity to regulate the glycaemia level.
When blood glucose is < 1 g/l, the liver uses
hexokinase to synthesize glucose-6-
phosphate, which is then hydrolysed by
means of glucose-6-phosphatase, resulting
in the release of glucose into the bloodstream
(glycogenolysis). Fatty deposits do not
increase in this situation but are, instead,
used for energy production.
The aim of our second study was to
evaluate whether chlorogenic acid enriched
Coffee Slender®(which is particularly rich in
chlorogenic acids, including 5-caffeoylquinic
acid) could reduce the weight of overweight
volunteers by causing the burning-off of fat,
as has been suggested by in vitro studies in
which inhibition of hepatic glucose-6-
phosphatase activity by 5-caffeoylquinic
acid has been shown.11,12
The significant decrease in body weight
and fat percentage with Coffee Slender®
compared with conventional instant coffee
could be due to an increase in the
consumption of fatty deposits, as shown by a
change in the fat mass percentage, and the
prevention of fatty deposits being
accumulated, as discussed above.
Chlorogenic acid might act by inhibiting
glucose absorption in the small intestine.10
In addition, inhibition of the activity of
glucose-6-phosphatase11,12 would limit the
release of glucose into the general
circulation15,16 and, therefore, limit
insulinaemia. This would lead to fewer fatty
deposits in the adipose tissue through harder
access into the adipose cells owing to reduced
insulin activity and the consumption of fat
reserves, due to the reduced availability of
glucose as an energy source.
This proposed mechanism, however,
depends on the bioavailability of
chlorogenic acid (5-caffeoylquinic acid).
Recently, its fate and metabolism were
explored to determine the form under which
this ester of caffeic acid is absorbed through
different parts of the gastrointestinal tract of
rats.17 Analysis of gastrointestinal contents
indicated that chlorogenic acid was stable in
the stomach and the small intestine, but was
cleaved into caffeic acid by microflora in the
caecum.17 Consequently, the stability of
chlorogenic acid in the small intestine is
coherent with glucose absorption inhibition
in this part of the gut. Moreover, whereas it
was shown that chlorogenic acid was
hydrolysed into enterocytes before secretion
on the serosal side,18 it was absorbed intact
from the stomach17 and was found in the
gastric vein and aorta without conjugation.
These results suggest that chlorogenic acid is
able to enter the liver without modification,
which is in accordance with its inhibitory
activity on hepatic glucose-6-phosphatase.
These bioavailability studies on chlorogenic
acid thus support the proposed mechanism
of action outlined above. These findings are
also consistent with recent studies of a link
between chlorogenic acid and body mass in
mice, which concluded that chlorogenic acid
can prevent an increase in body mass and
accumulation of fat.19
Published studies show that caffeine
intake may lead to a small reduction in long-
termweight gain.20 This effect is probably
due to the known thermogenetic effect of
caffeine intake as well the effect of
chlorogenic acid and other
pharmacologically active substances known
to be present in coffee. Coffee has been
shown to have positive effects on several
glycaemia markers: consumption is
significantly and inversely associated with
impaired fasting glucose, impaired glucose
regulation and hyperinsulinaemia in elderly
men and women.21

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•Received for publication 1 May 2007 • Accepted subject to revision 4 July 2007
•Revised accepted 4 October 2007
Copyright © 2007 Field House Publishing LLP
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Chlorogenic acid enriched coffee and glucose absorption
Any place that coffee products may have
in future treatments for overweight and
obesity will also depend on the clinical
conclusions to be drawn from studies
examining the association between coffee
and myocardial infarction in individuals
with ‘slow’ caffeine metabolism.22 The risk
factor might be as high as 60% in the total
Caucasian population. Chlorogenic acid
might also be partly responsible for raised
homocysteine concentrations that have been
observed in coffee drinkers.23 Whether these
effects on homocysteine influence
cardiovascular disease risk remains to be
established. It seems, however, that the
chlorogenic acid in green coffee bean extract
does not have the same effect on
homocysteine.24
Acknowledgement
The author is grateful to Berkem SA,
Gardonne, France, for providing the beans of
Coffea canephora robusta Pierre (Svetol®)that
were used in these two studies.
Conflicts of interest
No conflicts of interest were declared in
relation to this paper.

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Author’saddress for correspondence
Dr Erling Thom
ETC Research and Development, Stasjonsveien 5A, 0774 Oslo, Norway.
E-mail: erlingthom@etc.as
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